Psoralen plus long wavelength ultraviolet radiation (UV-A) is being investigated as a model system for clinically relevant photochemical carcinogenesis. Used experimentally for treatment of psoriasis and mycosis fungoides, psoralen plus UV-A has been found to be mutagenic in bacteria and carcinogenic in mice and humans. We have developed an in vitro assay to measure the effects of psoralen-DNA binding on human lymphoid cells. Parameters monitored include the rate of DNA synthesis, induction of DNA-psoralen cross-links, induced sister chromatid exhanges, alterations in the rate of cell proliferation and survival, and in immune reactivity. We are attempting to measrue psoralen-DNA antibodies in rabbits or humans for use as a cellular probe. These studies are aimed at understanding the mechanism of cell damage induced by psoralen plus UV-A so as to minimize the toxicity to human cells during therapy.